Human pancreatic islets are an essential and precious research resource that allows investigators to address basic science and clinical questions related to the prevention, treatment, and pathophysiology of diabetes mellitus. While experiments employing alternative cellular sources are yielding considerable data, studies in the last decade have established remarkable differences that emphasize the importance and irreplaceable nature of human islets. However, several challenges exist in establishing and maintaining the necessary infrastructure and coordinating functions to effectively and efficiently distribute this precious resource to islet research laboratories. City of Hope is applying to this UC4 mechanism to remain the coordinating center to support the Integrated Islet Distribution Program (IIDP) that provides for the distribution of human cadaveric islets for biomedical research. Our application leverages the significant investment made by NIH over the last decade that has established and successfully maintained this islet distribution network at City of Hope. As the ongoing Coordinating Center, we will continue to subcontract with qualified islet isolation facilities to prepare and distribute human islets with our support and advanced electronic data systems. Our Coordinating Center team will continue to manage the IIDP application process to establish eligibility to receive islets, maintain a roster of investigators approved to receive islets, and further enhance our Islet Allocation System that allows distribution centers to broadcast offers online and notifies approved waiting researchers of islet availability. We will continue the existing partial cost recovery system through subscription fees collected from islet researchers, which has successfully garnered $930,800 to help offset the expense of pancreas processing to date. We will continue to closely monitor and help to improve the quality of islets distributed, through our quality control panel and data, batch test release information, mandatory User Feedback Forms, and standardized operating procedures for processes such as islet counting and shipping. Through our proven state-of-the-art administrative, business, technical, statistical, and informatics processes and tools, this project will secure the accessibility of human islets for investigators conducting essential diabetes mellitus research. From qualification and auditing of high-quality suppliers to forecasting, tracking, and meeting the needs of investigators, our experienced City of Hope team proposed in this grant has worked with 19 different isolation laboratories to coordinate the distribution of nearly 160 million islet equivalents to 170 basic scientists over a period of 10 years, facilitatin the completion and publication of over 350 studies. If awarded this grant, our 3 aims described in this application will provide an indispensable research service to the diabetes research community by ensuring that the IIDP network remains stable, up-to-date technologically, continually enhanced with improved standardization and quality, and fully responsive to the islet needs of the community, thus promoting the next generation of scientific experimentation toward prevention and treatment of diabetes. PUBLIC HEALTH RELEVANCE: Individuals with diabetes experience significant primary and secondary complications, at a 2007 estimated annual cost of $174 billion dollars in the United States. The central importance of human islets in the pathology of this disease, and its demonstrated use as an unparalleled experimental and treatment resource, has led to an escalating demand for islet preparations. Maintenance of a large scale islet distribution network is critical to provide researchers with access to this precious resource, advancing the discoveries and progress in the field of diabetes mellitus research.